Preparation of tetrahydropyran-4-carboxylic acid and its esters

ABSTRACT

A process for preparing tetrahydropyran-4-carboxylic acid and its esters of the formula I ##STR1## (R=H, C 1  -C 8  -alkyl, C 3  -C 8  -cycloalkyl, aryl, C 7  -C 12  -alkylphenyl and C 7  -C 12  -phenylalkyl) by reacting 2,7-dioxaspiro[4.4]nonane-1,6-dione II ##STR2## with water or alcohols III 
     
         R--OH                                                      (III), 
    
     in the presence of acidic catalysts at from 150° to 350° C. and from 0.01 to 100 bar.

This is an application under 35 USC § 371 of PCT/EP 93/03670 filed Dec.23, 1993.

This is an application under 35 USC § 371 of PCT/EP 93/03670 filed Dec.23, 1993.

The present invention relates to a process for preparingtetra-hydropyran-4-carboxylic acid and its esters by reaction of2,7-dioxaspiro[4.4]nonane-1,6-dione with water or alcohols in thepresence of acidic catalysts at elevated temperatures.

From J. Chem. Soc. 1930, pages 2525 to 2530, a process for preparingtetrahydropyran-4-carboxylic acid esters is known in whichβ,β'-dichlorodiethyl ether is reacted with the sodium salt of diethylmalonate to give diethyl tetrahydropyran-4,4-dicarboxylate, and this isconverted to tetrahydropyran-4-carboxylic acid viatetrahydropyran-4,4-dicarboxylic acid and finally esterified to give thedesired tetrahydropyran-4-carboxylic acid ester.

EP-A-284 969 furthermore discloses preparingtetrahydropyran-4-carboxylic acid esters by reaction of3-(2-hydroxyethyl)butyrolactone or its esters and ethers with alcoholsin the presence of acidic catalysts.

A disadvantage of the known processes is that they proceed either innumerous reaction steps and with production of salt or only with lowyields.

It is an object of the present invention to make the compounds I moreaccessible.

We have found that this object is achieved by a novel and improvedprocess for preparing tetrahydropyran-4-carboxylic acid and its estersof the formula I ##STR3## where R is hydrogen, C₁ -C₈ -alkyl, C₃ -C₈-cycloalkyl, aryl, C₇ -C₁₂ -alkylphenyl or C₇ -C₁₂ -phenylalkyl, whichcomprises reacting 2,7-dioxaspiro[4.4]nonane-1,6-dione of the formula II##STR4## with water or alcohols of the formula III

    R--OH                                                      (III),

in the presence of acidic catalysts at from 150° to 350° C. and from0.01 to 100 bar.

The 2,7-dioxaspiro[4.4]nonane-1,6-dione II can preferably be reacted inmolten (m.p.: 108° to 109° C.) or dissolved form, together with thealcohol III or water and, if appropriate, an inert gas such as nitrogen,carbon dioxide or argon, to give tetrahydropyran-4-carboxylic acid andits esters I.

Reaction temperatures of from 200° to 300° C., in particular from 220°to 270° C. and a pressure of from 0.1 to 5 bar are particularlyadvantageous.

The reaction can be performed batchwise or continuously, eg. as asolid-bed reaction using solid-bed catalysts, for example in aliquid-phase or trickle procedure in the liquid or gas phase, eg. insolid form in a fluidized bed or with solid-bed catalysts suspended inthe liquid phase or homogeneous catalysts.

The material discharged from the reaction can be condensed by means of asuitable cooling device and then worked up by fractional distillation.The tetrahydropyran-4-carboxylic acid and its esters I can be separatedoff and unreacted 2,7-dioxaspiro-[4.4]nonane-1,6-dione II or the ethersor esters of 3-(2'-hydroxyethyl)dihydro-2(3H)furanone, eg.3-(2'-methoxyethyl)dihydro-2-(3H)-furanone, which may be contained inthe material discharged from the reaction, can be recycled (cf. EP-A-284963).

The reaction in the liquid phase can be carried out, for example, insuch a way that a mixture of 2,7-dioxaspiro[4.4]nonane-1,6-dione II andthe respective alcohol III (or water) is heated to the desired reactiontemperature in the presence of a suspended solid-bed catalyst or of ahomogeneous dissolved catalyst. After the necessary reaction time haspassed, the reaction mixture is cooled and the catalyst removed, eg. byfiltration or neutralization. The reaction mixture can then befractionally distilled to obtain the desiredtetrahydropyran-4-carboxylic acid ester.

The molar ratio of alcohol III or water to the2,7-dioxaspiro-[4.4]nonane-1,6-dione II is customarily from 0.5:1 to50:1, preferably from 1:1 to 30:1, particularly preferably from 2:1 to20:1.

In the case of heterogeneous catalysts, the reaction is carried out withcatalyst loadings of from 0.1 to 10, in particular from 0.1 to 5, g oflactone II per g of catalyst and hour.

Suitable alcohols of the general formula III are, for example, methanol,ethanol, n-propanol, isopropanol, tert-butanol, n-butanol, isobutanol,sec-butanol, n-pentanol, n-hexanol, phenol, cyclopentanol andcyclohexanol. Methanol, ethanol, n-propanol and isopropanol areparticularly suitable.

Suitable acidic catalysts are acidic homogeneous catalysts, in theliquid-phase reaction eg. mineral acids such as sulfuric acid,phosphoric acid, hydrochloric acid, nitric acid, hydrobromic acid orsulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid,but preferably heterogeneous catalysts, eg. acidic oxides of elements ofmain groups IIIA and IVA and of sub-groups IVB to VIB of the PeriodicTable of the Elements. Examples of acidic heterogeneous catalysts whichmay be mentioned are silica in the form of silica gel, kieselguhr,quartz, titanium dioxide, zirconium dioxide, vanadium pentoxide, borontrioxide, aluminum oxide, chromium oxides, molybdenum oxides, tungstenoxides, zeolites such as the Y zeolites or mixtures thereof. Phosphorouspentoxide can also be employed as an acidic catalyst. Aluminum oxide isparticularly preferred.

The molar ratio of acidic homogeneous catalyst to the2,7-dioxaspiro[4.4]nonane-1,6-dione II is normally from 0,001:1 to 1:1,preferably from 0.01:1 to 0.1:1.

The 2,7-dioxaspiro[4.4]nonane-1,6-dione II can be prepared, for example,according to J. Chem. Soc., Perkin I (1977), pp. 521-530 by reaction ofdiethyl malonate with ethylene carbonate in the presence of sodiumiodide, according to J. Org. Chem. Vol. 28 (1963), pp. 2809-2811 byhydrolysis of 1,5-dibromo-3,3-dicyanopentane with sulfuric acid oraccording to J. Org. Chem. Vol. 50 (1985), 1026-1031 by reaction ofmalonic acid with ethylene in the presence of manganese(III) acetate.

The substituent R in the compounds I and III has the following meanings:

R is

C₁ -C₈ -alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl,neopentyl, 1,2-dimethylpropyl, n-hexyl, isohexyl, sec-hexyl, n-heptyl,isoheptyl, n-octyl, isooctyl, preferably C₁ - to C₄ -alkyl such asmethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl andtertbutyl, particularly preferably methyl, ethyl, n-propyl andisopropyl,

C₃ -C₈ -cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl and cyclooctyl, preferably C₅ - to C₈-cycloalkyl such as cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl,particularly preferably C₅ - to C₇ -cycloalkyl such as cyclopentyl,cyclohexyl and cycloheptyl,

aryl such as phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl and9-anthryl, preferably phenyl, 1-naphthyl and 2-naphthyl, particularlypreferably phenyl,

C₇ -C₁₂ -alkylphenyl such as 2-methylphenyl, 3-methylphenyl,4-methylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl,2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl,2,3,4-trimethylphenyl, 2,3,5-trimethylphenyl, 2,3,6-trimethylphenyl,2,4,6-trimethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl,2-n-propylphenyl, 3-n-propylphenyl and 4-n-propylphenyl, preferably 2-and 4-methylphenyl,

C₇ -C₁₂ -phenylalkyl such as benzyl, 1-phenethyl, 2-phenethyl,1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-phenylbutyl,2-phenylbutyl, 3-phenylbutyl and 4-phenylbutyl, preferably benzyl,1-phenethyl and 2-phenethyl.

The tetrahydropyran-4-carboxylic acid esters obtainable by the processaccording to the invention are useful intermediates which can beprocessed, eg. to give tetrahydropyran-4-carbaldehyde (cf. DE-A-31 21355, DE-A-33 14 816, DE-A-33 40 265, DE-A-38 21 197 and DE-A-40 39 918).

PREPARATION EXAMPLE

22 g per hour of a 20% strength solution of2,7-dioxaspiro-[4.4]nonane-1,6-dione in methanol were added dropwise toa perpendicular tubular reactor via a heated dropping funnel (50° C.).10 l/h of nitrogen were additionally metered in. In the upper part thereactor contained quartz rings and below 43 g of Al₂ O₃ as a catalystand was operated at 230° C. The gaseous material discharged from thereaction was condensed in cooling traps and analyzed by gaschromatography.

In this reaction 40 mol % of methyl tetrahydropyran-4-carboxylate, 33mol % of 3-(2-methoxyethyl)dihydro-2(3H)furanone (recyclable by-product)and 14 mol % of 5-oxaspiro[2.4]heptan-4-one were formed. The methyltetrahydropyran-4-carboxylate selectivity was therefore 60%.

We claim:
 1. A process for preparing tetrahydropyran-4-carboxylic acidand its esters of the formula I ##STR5## where R is hydrogen, C₁ -C₈-alkyl, C₃ -C₈ -cycloalkyl, aryl, C₇ -C₁₂ -alkylphenyl or C₇ -C₁₂-phenylalkyl, which comprises reacting2,7-dioxaspiro[4.4]nonane-1,6-dione of the formula II ##STR6## withwater or alcohols of the formula III

    R--OH                                                      (III),

in the presence of acidic catalysts at from 150° to 350° C. and from0.01 to 100 bar.
 2. A process for preparing tetrahydropyran-4-carboxylicacid and its esters of formula I as defined in claim 1, wherein thereaction is carried out at from 200° to 300° C.
 3. A process forpreparing tetrahydropyran-4-carboxylic acid and its esters of formula Ias defined in claim 1, wherein the reaction is carried out at from 220°to 270° C.
 4. A process for preparing tetrahydropyran-4-carboxylic acidand its esters of formula I as defined in claim 1, wherein the acidiccatalysts used are acidic oxides of elements of main groups IIIA and IVAand of sub-groups IVB to VIB of the Periodic Table of the Elements.
 5. Aprocess for preparing tetrahydropyran-4-carboxylic acid and its estersof formula I as defined in claim 1, wherein the catalyst used isaluminum oxide.